We spend a third of our life asleep, and even partial sleep deprivation has serious consequences on cognition, mood, and health, suggesting that sleep must serve some fundamental functions. Unfortunately, we lack a neurobiological understanding of what these functions might be. However, we know that sleep is tightly regulated as a function of prior wakefulness, suggesting that it may be needed to reverse some changes that take place when we are awake. We also know that the organ that has the greatest need for sleep is the brain, although we still do not know why. The overall goal of this project is to test a recent, comprehensive hypothesis about thefunction of non-rapid eyemovement sleep - the synaptic homeostasis hypothesis. According to the hypothesis, the brain needs to sleep because of the progressive strengthening of neural circuits that occurs during wakefulness and the associated energy and performance costs. We will test some key prediction of the hypothesis by using a novel method for performing high-density sleep electroencephalography (hd-EEG, 256 channels). We will take advantage of the well-known fact that sleep need is reflected by the amount of slow wave activity (SWA) in the sleep EEG. Specifically, we will test the prediction that procedures leading to local increases in synaptic strength, such as learning tasks involving particular brain regions, should lead to a local increase in sleep SWA. We will use both an implicit learning task (rotation adaptation) involving right parietal cortex, and an explicit learning task involving prefrontal cortex (motor sequence learning). We will then test the converse prediction that procedures leading to a local depression of synaptic circuits, such as arm immobilization, should lead to a local decrease in SWA during subsequent sleep. If these predictions are confirmed, they will provide strong evidence that sleep SWA is regulated at a local level, that its regulation is tied to plastic changes in cortical circuits, and that the level of local SWA has important consequences on performance after sleep. The results provided by this project will lend strong support to the synaptic homeostasis hypothesis and greatly advance our understanding of the functions of sleep at the fundamental level. There is overwhelming evidence that good, restorative sleep is exceedingly important to human health, that sleep deprivation and sleep restriction have enormous social costs, that sleep disorders are extremely common, and that they are frequently associated with psychiatric and neurological disorders. By tying brain plasticity to local sleep regulation, the results of these investigations will provide a novel, rational basis for designing therapeutic approaches aimed at enhancing the restorative value of sleep in health and disease. Thus, they are highly relevant to the mission of MINDS, NIMH, and NHLBI.